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Liposomal Irinotecan, 5-FU, Leucovorin, and Paricalcitol in Treating Patients with Advanced Unresectable Pancreatic Cancer That Has Progressed on Gemcitabine-Based Therapy

Trial Status: Active

This phase I trial studies the best dose and side effects of paricalcitol when given together with liposomal irinotecan, 5-FU, and leucovorin in treating patients with pancreatic cancer whose disease has progressed on therapy containing gemcitabine, and that has spread to other places in the body (advanced) and cannot be removed by surgery (unresectable). Paricalcitol is currently used to prevent and treat hyperparathyroidism associated with chronic kidney disease. It may promote tumor cell death by acting on some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as liposomal irinotecan, 5-FU and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This study may help researchers determine what the recommended dose of paricalcitol is when given with liposomal irinotecan, 5-FU, and leucovorin.

Inclusion Criteria

  • Histologically or cytologically confirmed pancreatic adenocarcinoma
  • Must have progressed on or become intolerant to gemcitabine-containing therapy in the advanced setting (not resectable). This is intended to be a second-line trial
  • Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with computed tomography (CT) scan, as >= 20 mm by chest x-ray, or >= 10 mm with calipers by clinical exam
  • Life expectancy > 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9 g/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Serum albumin >= 3 g/dL
  • Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (IULN) unless there are liver metastases, in which case AST and ALT =< 5.0 x IULN
  • Creatinine =< 1.5 x IULN OR glomerular filtration rate (GFR) > 50 mL/min
  • Corrected calcium =< 10.3 mg/dL
  • Phosphorus =< 4.5 mg/dL
  • Patients will require a 2-week washout period from previous gemcitabine-based systemic therapy, a 2-week washout period from previous radiation therapy, and a 4-week washout period from surgery prior to the first planned dose of study treatment
  • Prior treatment-related toxicity must recover to grade 1 or less prior to the first planned dose of study treatment
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
  • Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria

  • More than one prior systemic treatment in the advanced setting. Disease recurrence within 6 months of adjuvant therapy is considered one line of systemic treatment
  • Patients with active renal, ureteral, or bladder stones on the screening imaging
  • Current use of or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment
  • A history of other malignancy within 2 years previous, with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only, or carcinoma in situ of the cervix
  • Currently receiving any other investigational agents
  • Patients who received fluorouracil, irinotecan, leucovorin and oxaliplatin (FOLFIRINOX) or leucovorin calcium, fluorouracil, and irinotecan (FOLFIRI) in the neoadjuvant or adjuvant setting who experienced disease recurrence within 6 months will be excluded (patients who received 5-FU or capecitabine as a radiosensitizer are permitted to enroll.)
  • Patients with known active/ progressive brain metastases or leptomeningeal involvement will be excluded due to their poor prognosis. Patients with treated/stable brain metastases, defined as patients who have received prior therapy for their brain metastases and whose central nervous system (CNS) disease is radiographically stable at study entry, are eligible
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to paricalcitol, liposomal irinotecan, 5-FU, LV, or other agents used in the study
  • Clinical significant ascites that requires therapeutic paracentesis or significant pleural effusion that requires therapeutic thoracentesis
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry
  • Known human immunodeficiency virus (HIV)-positivity not on anti-retroviral therapy, or with CD4+ T cell count < 200/ul (patients with known HIV currently on anti-retroviral therapy with CD4+ T cell count > 200/ul will be included)

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE
Contact: Andrea Wang-Gillam
Phone: 314-362-5740

PRIMARY OBJECTIVE:

I. To evaluate the tolerability between two different dose levels of paricalcitol added to the combination regimen of liposomal irinotecan plus fluorouracil (5-FU)/leucovorin calcium (LV) in patients with advanced pancreatic cancer.

SECONDARY OBJECTIVES:

I. To determine the overall response rate (ORR) of patients with advanced pancreatic cancer treated with the combination of paricalcitol added to liposomal irinotecan plus 5-FU/LV.

II. To determine the progression free survival (PFS) of patients with advanced pancreatic cancer treated with the combination of paricalcitol added to liposomal irinotecan plus 5-FU/LV.

III. To determine overall survival (OS) of patients with advanced pancreatic cancer treated with the combination of paricalcitol added to liposomal irinotecan plus 5-FU/LV.

IV. To determine the CA19-9 biochemical response rate of patients with advanced pancreatic cancer treated with the combination of paricalcitol added to liposomal irinotecan plus 5-FU/LV.

V. To determine the duration of overall response of patients with advanced pancreatic cancer treated with the combination of paricalcitol added to liposomal irinotecan plus 5-FU/LV.

VI. To determine the duration of complete response of patients with advanced pancreatic cancer treated with the combination of paricalcitol added to liposomal irinotecan plus 5-FU/LV.

VII. To determine the duration of stable disease of patients with advanced pancreatic cancer treated with the combination of paricalcitol added to liposomal irinotecan plus 5-FU/LV.

CORRELATIVE OBJECTIVES:

I. To identify molecular and genetic predictors of response to the combination regimen.

II. To identify alterations in tumor stroma and tumor immune infiltrate secondary to paricalcitol.

OUTLINE:

Patients receive paricalcitol intravenously (IV) on days 1 and 8 for up to 10 cycles. Patients also receive liposomal irinotecan IV over 90 minutes, leucovorin calcium IV over 30 minutes and fluorouracil IV over 46 hours on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Andrea Wang-Gillam

  • Primary ID 201905201
  • Secondary IDs NCI-2019-04360
  • Clinicaltrials.gov ID NCT03883919